Epigenetic inactivation of SOCS‐1 by CpG island hypermethylation in human gastric carcinoma

Abstract Suppressor of cytokine signaling (SOCS)‐1 inhibits signaling of the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway by several cytokines and has tumor suppressor activity. Methylation of the SOCS‐1 CpG island has been shown to inactivate the SOCS‐1 gene in certain human cancers. In our study, we investigated methylation status of the SOCS‐1 gene by methylation‐specific PCR in 75 gastric carcinoma (GC) tissues, 25 corresponding nonneoplastic mucosae and 10 normal gastric mucosae from healthy young individuals. We also performed bisulfite sequencing of DNAs from 2 GC tissues. In addition, SOCS‐1 mRNA levels were examined in 50 GCs by quantitative RT‐PCR. Hypermethylation of the SOCS‐1 gene was detected in 33 (44%) of 75 GC tissues and in 3 (12%) of 25 corresponding nonneoplastic mucosae; the incidence was significantly different ( p = 0.004). None of the 10 normal gastric tissues from healthy individuals showed hypermethylation. Methylation of the SOCS‐1 gene was associated with lymph node metastasis, advanced tumor stage and reduced expression of SOCS‐1 in GC tissues ( p = 0.009, 0.034 and 0.002, respectively). Reduced expression of SOCS‐1 in GC tissues was associated with lymph node metastasis and advanced tumor stage ( p = 0.013 and 0.002, respectively). Our results suggest that transcriptional inactivation of the SOCS‐1 gene by hypermethylation may be involved in development, progression and metastasis of GC. © 2004 Wiley‐Liss, Inc.